Abstract: The overall aims of this project are to explore the effects of multiple levels of racism on the immune function, and overall health of urban African Americans, and to test a novel structural-level intervention to reduce the negative impact of racism. Significant disparities in major chronic illnesses continue to describe the current picture of health for African Americans, including cardiovascular disease, cancer, and overweight/obesity. Researchers have long understood stress to play a critical role in negative health outcomes, and particular attention has been paid to the hypothalamic-pituitaryadrenocortical (HPA) axis as a key pathway. Because experiences with racism constitute a significant stressor in the lives of African Americans, understanding the ways in which racism activates the axis will have profound meaning in addressing the determinants of African American health disparities. More broadly, given the role of the HPA axis in many systems, the proposed research has the potential to uncover critical information on the impact of social processes on overall physical and mental health, and to delineate unstudied paths in brain-behavior relationships. In two sub-studies, the proposed research will enroll urban African Americans from New York City in longitudinal investigations. Study 1 is an investigation of how neighborhood-level institutional racism and perceived individual and collective racism affect immune and metabolic function and overall physical health, psychological well-being, and health behaviors. Study 2 is neighborhood-level intervention to minimize the likelihood of internalized racism, vis-[unreadable]vis a racism "countermarketing" campaign. Outdoor advertising will be employed to deliver stark facts about American inequality in predominantly African American neighborhoods, thereby raising consciousness and minimizing negative health outcomes. Taken together, the proposed research attempts to answer two critical unanswered questions in biomedical and behavioral research: 1) How does racism get into the body?;and 2) What do we do about it? Public Health Relevance: Although racism is well known to be a significant life stressor for African Americans, no research has studied the effects racism has on critical biological pathways, such as immune function. Additionally, although other negative effects of racism have been documented, no study has yet created a broad-based intervention to counter the stress of racism on African American lives. The proposed study will do both, which could have a major impact on the reduction of African American health disparities.